Global Burden of Congenital Infections Affecting Fetal Brain Structure and Neurodevelopment: A Systematic Review and Meta-Analysis

Abstract

Background: Congenital TORCH infections, including both traditional and emerging
pathogens such as Zika virus and Parvovirus B19, represent a major and heterogeneous global
cause of fetal brain injury and long-term neurodevelopmental impairment. However, the
collective burden and variability of structural and functional outcomes across these infections
have not yet been comprehensively synthesized.
Methods: This systematic review and meta-analysis was conducted following PRISMA 2020
guidelines and registered with PROSPERO (CRD420261366077), searching PubMed, Europe
PMC, Google Scholar, and major medical databases for observational studies published
between 2016 and 2026. Data extraction and quality assessment using the Joanna Briggs
Institute (JBI) Critical Appraisal Checklist were performed independently by two reviewers,
with pooled prevalence estimated using a random-effects model and Freeman–Tukey
transformation, supplemented by subgroup analyses across infection types and country income
levels.
Results: Fifteen studies comprising 1,930 participants were included. Structural abnormalities
were reported more consistently than neurodevelopmental outcomes. The pooled prevalence
of microcephaly was 11% (95% CI: 5–24%), ventriculomegaly 14% (8–28%), intracranial
calcification 19% (11–31%), white matter injury 18% (9–35%), and cortical abnormalities 7%
(3–15%). Among neurodevelopmental outcomes, hearing loss (23%, 14–35%) and
developmental delay (20%, 14–27%) were most common. Outcome patterns were strongly
pathogen-specific, with Zika virus associated with microcephaly and CMV with hearing loss.
Differences between income groups were inconsistent and likely influenced by geographic
clustering of infections and diagnostic variability
Conclusion: Congenital TORCH infections represent a major and heterogeneous cause of fetal
brain injury and neurodevelopmental impairment, driven by distinct pathogen-specific
mechanisms. These findings emphasized the need for improved risk stratification, early
detection, and targeted clinical management to mitigate long-term outcomes.